Reagents in Organic Synthesis DR.S.D.PATIL Associate Professor in Chemistry Shivraj College Gadhinglaj.

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Reagents…… In organic chemistry, reagents are compounds or mixtures, usually composed of inorganic or small organic molecules, that are used to effect a transformation on an organic substrate. A substance used in a chemical reaction to detect, measure, examine, or produce other substances. A substance used in a chemical reaction to detect, measure, examine, or produce other substances.

Unit II. Reagents in Organic Synthesis. [06] Preparation and Applications of following reagents. 1. Lithium aluminium hydride LiAlH4 2. Osmium tetraoxide 3. Dicyclohexyl Carbodiimide (DCC) 4. Raney Nickel 5. 2,3-Dichloro -5,6-dicyano – 1,4-benzoquinone (DDQ) 6. Polyphosphoric acid (PPA) 7. Diazomethane 8. Cerric ammonium nitrate (CAN) 9. N-Bromosuccinamide (NBS) 10.Selenium dioxide (SeO2)

1. Lithium aluminium hydride

Lithium aluminium hydride • Lithium aluminium hydride, commonly abbreviated to LAH, is an chemical formula LiAlH4. • It was discovered by Finholt, Bond and Schlesinger in 1947. • This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters, carboxylic acids, and amides. T • he solid is dangerously reactive towards water, releasing gaseous hydrogen (H2)

Preparation…. 4 LiH + AlCl3 → LiAlH4 + 3 LiCl Industrial synthesis Na + Al + 2 H2 → NaAlH4 LiAH is then prepared by a salt metathesis reaction NaAlH4 + LiCl → LiAlH4 + NaCl LiCl is removed by filtration from an ethereal solution of LiAH, with subsequent precipitation of LiAH to yield a product containing around 1% w/w LiCl.

Name of Reagent Preparation Use

LiAlH4 LiH + AlCl3 Reducing agent for carbonyl compounds .. Acids, ketones, esters, anhydrides

2. Osmium tetroxide

Osmium tetroxide • Osmium tetroxide is the chemical compound with the formula OsO₄. It is volatile solid. • Formula: OsO4 • Molar mass: 254.23 g/mol • Density: 4.91 g/cm³ • Boiling point: 129.7 °C • Melting point: 40.25 °C

Preparation…. OsO4 is formed slowly when osmium powder reacts with O2 at ambient temperature. Reaction of bulk solid requires heating to 400 °C Os+ 2O2 → OsO4

• Alkenes add to OsO4 to give diolate species that hydrolyze to cis-diols. • The net process is called dihydroxylation. This proceeds via a [3 + 2] cycloaddition reaction between the OsO4 and alkene to form an intermediate osmate ester which rapidly hydrolyses to yield the vicinal diol. • As the oxygen atoms are added in a concerted step the resulting stereochemistry is cis

This process is extended to give to aldehydes in the Lemieux–Johnson oxidation, which uses periodate to achieve diol cleavage and to regenerate the catalytic loading of OsO4. This process is equivalent to that of ozonolysis.

Name of Reagent Preparation Use

OsO4 Os+ 2O2 Cis hydroxylation of olefinic double bond

3. Dicyclohexylcarbodiimide DCC

• DCC is a dehydrating agent often used to form esters, amides or anhydrides. • It is commercially available as a waxy lowmelting solid (34-35°C). • It can also be prepared by oxidation of dicyclohexylurea with p -toluenesulfonyl chloride in hot pyridine or • By heating dicyclohexylthiourea with yellow mercuric oxide (Scheme 1). The section covers some important applications in organic synthesis.

DCC Preparation…

Name of Reagent Preparation

Use

DCC Dicyclohexylurea Dicyclothiourea Dehydrating agent

4. Raney Nickel • Raney nickel is a fine-grained solid composed mostly of nickel derived from a nickel-aluminium alloy. • In the activation process, the alloy, usually as a fine powder, is treated with a concentrated solution of sodium hydroxide. 2 Al + 2 NaOH + 6 H2O → 2 Na[Al(OH)4] + 3 H2 This gives sodium meta aluminate • Raney nickel is used as a reagent and as a catalyst in organic chemistry.

• Murray Raney (October 14, 1885 – March 3, 1966) was an American mechanical engineer. • He was the developer of a nickel catalyst that became known as Raney nickel, • It is often used in industrial processes and scientific research for the hydrogenation of multiple covalent bonds.

Reactions - Raney Nickel

Name of Reagent Preparation Use

Raney Nickel Ni-Al alloy and NaOH Reducing agent for alkenes, phenols and other aromatic compounds

5. DDQ 2,3-Dichloro-5,6-dicyano1,4-benzoquinone

Cyanation of chlotanil

DDQ - 2,3-Dichloro-5,6dicyano-1,4-benzoquinone • Formula C₆Cl₂(CN)₂O₂. • This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones in organic chemistry. •Density: 1.70 g/cm³ •Boiling point: 301.8 °C

Reactions of DDQ

Tetralin to naphthalene Using DDQ

Reactions of DDQ

Name of Reagent Preparation Use

DDQ Benzquinone or chloranil Oxidising agent for organic syntheses.

6. Polyphosphoric acid PPA

Preparation….. Phosphoric acid is produced industrially by two general routes – the thermal process and the wet process. Wet process phosphoric acid is prepared by adding sulfuric acid to tricalcium phosphate rock, typically found in nature as apatite. The reaction is: Ca5(PO4)3X + 5 H2SO4 + 10 H2O → 3 H3PO4 + 5 CaSO4·2 H2O + HX where X may include OH, F, Cl, and Br

Preparation….. Laboratory routes A demonstrative process consists in the oxidation of red phosphorus by nitric acid.

1/ n

Pn + 5 HNO3 → H2O + H3PO4 + 5 NO2

Name of Reagent Preparation

Uses

PPA sulfuric acid to tricalcium phosphate Dehydrating drying agent To make phosphate esters, acid phosphates and pharmaceuticals. Ring closing reagent. Solvent PPA is used in metal treatment and as an asphalt and bitumen additive.

7. Diazomethane CH2N2

Diazomethane is prepared by hydrolysis of an ethereal solution of an N-methyl nitrosamide with aqueous base.

Reactions of CH2N2

9. N-Bromosuccinimide NBS

N-Bromosuccinimide or NBS is a reagent used in radical substitution and electrophilic addition reactions in organic chemistry. NBS can be a convenient source of Br•, the bromine radical.

Preparation….. It is synthesized in the laboratory by adding sodium hydroxide and bromine to an icewater solution of succinimide. The NBS product precipitates out and can be collected by filtration.

NBS Reactions

Addition to alkenes

NBS Reactions

With the addition of nucleophile, instead of water, various bifunctional alkanes can be synthesized

NBS Reactions

Bromination of carbonyl derivatives

10.Selenium dioxide (SeO2)

10.Selenium dioxide (SeO2)

SeO2 is an important oxidizing reagent in organic synthesis.

Preparation ….. Selenium dioxide is prepared by 1.Oxidation of selenium by burning in air and nitric acid 3 Se + 4 HNO3 + H2O → 3 H2SeO3 + 4 NO

2. Reaction with hydrogen peroxide. 2 H2O2 + Se → SeO2 + 2 H2O 3. The most convenient preparation is by the dehydration of selenous acid. H2SeO3 ⇌ SeO2 + H2O

Awards and Recognition

Dr. S. D. Patil was awarded Sant Tukadoji Maharaj Best Popular Science Book award by Government of Maharashtra for his Marathi Book Deshodeshiche Vidnyaneshwar (2009).

304 B 207 Deshodeshiche Vidnyaneshwar Dr. Ajit Patil Maharashtra Govt Jan-11

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Monday, 4 October, 2010 1:52 AM Dear Professor Ajit Patil , How are you doing ? We are doing fine on our side . We will be in Pune from Jan 7 to Mar 20 , 2011 .

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I have almost finished reading your remarkable , stimulating and highly informative book and have recommended it to our Marathi Book Club here in West Windsor , NJ . Accordingly we started reading it in the Book Club last week and the members appreciate the book very much .

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One of the members , Ashok Vidwans may contact you on tel or E-mail about a reference which you have given in the article on Bhakaracharya . In anticipation of your approval I have given him your cell tel no. and your Email address . Please convey my regards to Professor Kurade-Patil , Pricipal Jodgudri and Professor Khichadi .

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With regards to you , Vijay V Joshi , MD , PhD , FRC Path .

Published Book on the great scientist Marie Curie to salute her in the International Year of Chemistry (IYC)- 2011

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